Herpesviruses are relatively common causes of infections in immuno- compromised hosts such as cancer patients, and have been implicated in certain neoplasias. Herpes virus hominis type 2 (HSV-2) has been assocated with cervical carcinoma in humans and mice The various aspects of host responses that might influence whether herpesvirus type 2 infection is severe, clinically inapparent, or latent and potentially oncogenic have not been delineated. In this research program, we plan to evaluate the relative roles and interactions among components of the immune system (cellular immunity, antibody, macrophage activity, interferon) to systemic infection of female mice with HSV-2. The overall plan is to initiate intraperitoneal or intragenital infection with HSV-2 in normal female mice, in mice that have been selectively depleted of thymys-depenent lymphocytes or macrophages, and in these immunologically depleted mice that have been specifically reconstituted with normal or immune cells The effects on the pathogenesis and persistence of HSV-2 in vivo will be assessed in conjunction with measurement of various immune responses to HSV-2 in vivo and in vitro. Once the initial pathogenesis and immunity studes are well underway, the long er goals of this research program will also include determination of the mode of anti-herpetic action of certain immunoadjuvants that would be potentially useful clinically in immunosuppressed patients. These studiesshould establis whether certain immunoadjuvant drugs are effective against herpesvirus infection in an immuno-compromised host, and outline the mchanism of interaction of such drus with the immune system. This investigation should indicate a rationale for more effective use of immunoadjuvants that may be relevant to immunotherapy of certain human viral infections or neoplasia.